NOLASIBAN for Infertility (indication for IVF/ICSI)

Inclusion criteria

• {"criterion_text":"- 1. Signed informed consent related to trial participation prior to any trial-related activity.\n- 2. In good physical and mental health in the judgement of the investigator.\n- 3. Women between the ages of 18 and 42 years. The participants must be at least 18 years (including the 18th birthday) when they sign the informed consent and no more than 42 years (up to the day before the 43rd birthday) at the time of randomization.\n- 4. Body mass index (BMI) between 18.5 and 35.0 kg/m2 (both inclusive) at screening.\n- 5. Infertile women diagnosed with tubal infertility, unexplained infertility, or with partners diagnosed with male factor infertility, eligible for in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI). Women without a male partner (including single or same-sex female couples) may be included if they are considered eligible for IVF/ICSI as per standard clinical practice.\n- 7. Willing and able to comply with trial procedures, including attending scheduled visits.\n- 6. Agreement from the participant to use barrier contraception (male condom) during vaginal intercourse, or to remain abstinent from vaginal intercourse, from the start of estradiol provided as NIMP to the end-of-trial visit."}

Exclusion criteria

• {"criterion_text":"- 1. Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events.\n- 10. Known abnormal cervical cytology of clinical significance observed within three years prior to randomization (unless the clinical significance has been resolved).\n- 11. Known cervical stenosis.\n- 2. Known inherited or acquired thrombophilia.\n- 20. Known history of difficult transfer in a fresh or frozen embryo transfer cycle or known history of difficulties during an intrauterine insemination procedure, i.e., uterine sounding or cervical dilatation required.\n- 22. Pregnancy (negative urinary pregnancy test must be documented on Day 1, prior to any IC-EHG assessment).\n- 23. Currently breast-feeding.\n- 24. Currently using hormonal contraception, including combined estrogen- and progestogen-containing methods (oral [except for cycle programming], intravaginal, or transdermal), progestogen-only methods (oral, injectable, or implantable), or an intrauterine hormone-releasing system (IUS), or using an IUD.\n- 25. Undiagnosed vaginal bleeding.\n- 26. Known current or recent (within 6 months prior to screening) cardiovascular event, defined as: a. Myocardial infarction or unstable angina. b. Coronary artery bypass surgery, balloon angioplasty, percutaneous coronary intervention or carotid revascularization procedure. c. Uncontrolled hypertension. d. Significant cardiac arrhythmia. e. Endovascular procedure or surgical intervention for peripheral vascular disease. f. Advanced ischemic heart disease. g. Congestive heart failure (New York Heart Association [NYHA] III/IV).\n- 27. Likely to require treatment with systemic (oral, intravenous, and intramuscular) glucocorticoids in doses equivalent to more than 5 mg of prednisone from screening until the end-of-trial visit.\n- 10. Known current active pelvic or uterine infection (such as endometritis, cervicitis, or pelvic inflammatory disease).\n- 28. Likely to require treatment with magnesium sulphate (MgSO4) from screening until the end-of-trial visit.\n- 29. Likely to require treatment with any of the medications prohibited from screening and until the end-of-trial visit: a. Medications with utero-relaxant properties, such as calcium channel blockers (ATC code C08), beta-sympathomimetic agonists (ATC code R03), nitroglycerin (ATC code C01D), magnesium sulphate (ATC code B05X), potassium channel openers (ATC code C02D) and drugs for functional gastrointestinal disorders (ATC code A03), as these could interfere with evaluation of the investigational medicinal product. Note: this criterion does not apply to the progesterone provided as non-investigational product during the mock cycle. b. Medications with uterotonic properties, such as dopamine (ATC code C01C), progesterone antagonists (ATC code G03XB) and prostaglandin analogues (ATC code A02B) that could interfere with evaluation of the investigational medicinal product. c. Anxiolytics (ATC code N05B), hypnotics and sedatives (ATC code N05C) or continuous use of non-steroid anti-inflammatory drugs (NSAIDs), including aspirin. d. Medications that are sensitive substrates of transport proteins P-gp/MDR1, BCRP, OAT3, or OATP1B1, such as: • P-gp/MDR1: digoxin, dabigatran etexilate, fexofenadine, loperamide, apixaban • BCRP: rosuvastatin, sulfasalazine • OAT3: furosemide, adefovir • OATP1B1: rosuvastatin, pravastatin, atorvastatin, simvastatin e. Medications that are sensitive substrates of CYP1A2, CYP2B6, or CYP3A4, such as: • CYP1A2: theophylline, clozapine, tizanidine • CYP2B6: bupropion, methadone, ketamine • CYP3A4: midazolam, simvastatin, lovastatin, triazolam, buspirone Note: for CYP3A4, an exception is made for the estrogen and progesterone provided as NIMPs during the trial.\n- 30. Known history of chemotherapy (except for gestational conditions) or radiotherapy.\n- 3. Any known endocrine or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) with the exception of pharmacologically controlled sub-clinical hypothyroidism and insulin resistance.\n- 31. Current or past (1 year prior to randomization) abuse of alcohol or drugs.\n- 32. Current (last month) intake of more than 14 units of alcohol per week (one unit is equivalent to approximately 350 mL of regular beer [5% alcohol], 150 mL of wine [12% alcohol], or 40 mL of 80 proof distilled spirits [40% alcohol].\n- 33. Current or past (3 months prior to randomization) smoking habit of more than 10 cigarettes per day.\n- 34. Known hypersensitivity to any active ingredient or excipients in the medicinal products used in this trial.\n- 35. Known allergy to peanuts or soy.\n- 36. Any known clinical condition that would prevent the use of estrogen or progestin compounds.\n- 11. Any abnormal finding at the assessment of vital signs at screening, which is judged clinically significant by the investigator.\n- 37. Previous randomization in this trial.\n- 38. Use of any non-registered investigational drugs during the last 3 months prior to randomization.\n- 39. Current participation in another trial, including a participant follow-up period.\n- 4. Known tumors of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus.\n- 5. Known porphyria.\n- 6. Known jaundice.\n- 7. Known moderate or severe impairment of adrenal function.\n- 8. Known moderate or severe impairment of renal or hepatic function.\n- 9. Any of the following laboratory parameters at screening: a. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 times the upper limit of normal (ULN) or bilirubin ≥2 times the ULN (unless caused by Gilbert Syndrome). b. Estimated glomerular filtration rate (eGFR) <60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] 2021 equation) or serum creatinine >ULN and considered clinically significant by the investigator. c. Urine dipstick U-Protein ≥1+, confirmed by: - Albumin:creatinine ratio (ACR) >300 mg/g (>30 mg/mmol), or - Protein:creatinine ratio (PCR) ≥500 mg/g (≥50 mg/mmol).\n- 21. Currently in an active reproductive cycle. For these purposes, an “active reproductive cycle” shall be understood as any stage of care in which a clinical intervention is ongoing or planned for immediate implementation for reproductive purposes, including, among others, ovarian stimulation, in vitro fertilization (IVF) procedures or similar techniques, as well as the availability of embryos with a scheduled or pending transfer. Routine follow-up after completion of reproductive treatments shall not be considered an “active cycle”, provided that there is no immediate plan for new interventions.\n- 12. Evidence of any of the following at screening or within 1 year prior to screening that remains unresolved: a. Uterine fibroids defined as submucous fibroids of any size. b.\tIntramural fibroids larger than 3 cm in diameter or protruding into the uterine cavity. c. Uterine polyps. d. Congenital or acquired uterine anomalies that could interfere with the recording of uterine contractility.\n- 13. Failure to obtain an adequate IC-EHG recording after up to two attempts on Day 1 (pre-dosing).\n- 14. Known previous uterine surgery (such as myomectomy or cesarean section).\n- 15. Known recent intrauterine procedures (such as hysteroscopy or intrauterine device [IUD] removal) within the past 30 days.\n- 16. Known history of uterine artery embolization or radiofrequency ablation.\n- 17. Suspicion of endometrial hyperplasia or intrauterine adhesions."}

Primary endpoints

• {"endpoint_text":"- Change in uterine contractility index from Day 1 to Day 4 of treatment","definition_or_measurement_approach":"Change in uterine contractility index measured by IC-EHG recording (IC-EHG assessments pre-dosing on Day 1 and Day 4)."}

Methods

• Recruitment materials available: K2_Recruitment material - referral letter_public (referral letters) and K2_Recruitment material - advertisement text_public (advertisement text) — materials for recruiting eligible infertile women (indication for IVF/ICSI) via fertility clinics/sites.
• Site-based recruitment at participating fertility clinics/IVF centres in Spain (sites listed in Spain Part II).

Spain

Earliest CTIS Part Ii Submission Date

21-04-2026

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

20

Number Of Sites

5

Number Of Participants

120

Primary sponsor

Full Name

ReproNovo ApS

Organisation Type

Pharmaceutical company

Country Of Registered Address

Denmark